1. Folate‐mediated one‐carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women's Health Initiative Observational Study
- Author
-
Cheng, Ting-Yuan David, Makar, Karen W, Neuhouser, Marian L, Miller, Joshua W, Song, Xiaoling, Brown, Elissa C, Beresford, Shirley AA, Zheng, Yingye, Poole, Elizabeth M, Galbraith, Rachel L, Duggan, David J, Habermann, Nina, Bailey, Lynn B, Maneval, David R, Caudill, Marie A, Toriola, Adetunji T, Green, Ralph, and Ulrich, Cornelia M
- Subjects
Cancer ,Digestive Diseases ,Colo-Rectal Cancer ,Nutrition ,Genetics ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Aged ,Biomarkers ,Case-Control Studies ,Colorectal Neoplasms ,DNA-Binding Proteins ,Female ,Ferredoxin-NADP Reductase ,Folic Acid ,Genetic Predisposition to Disease ,Histone-Lysine N-Methyltransferase ,Humans ,Logistic Models ,Methylenetetrahydrofolate Dehydrogenase (NADP) ,Middle Aged ,Minor Histocompatibility Antigens ,Nuclear Proteins ,Polymorphism ,Single Nucleotide ,Postmenopause ,Risk Assessment ,Transcription Factors ,Vitamin B Complex ,biomarker ,colorectal cancer ,gene-nutrient interaction ,one-carbon metabolism ,postmenopausal women ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundInvestigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations.MethodsTwo hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5'-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at the baseline. Conditional logistic regression was implemented; effect modification was examined on the basis of known enzyme-nutrient relations.ResultsStatistically significant associations were observed between CRC risk and functionally defined candidate SNPs of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1; K134R), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; P450R), and PR domain containing 2 with ZNF domain (PRDM2; S450N) and a literature candidate SNP of thymidylate synthase (TYMS; g.676789A>T; nominal P
- Published
- 2015